Coeliac Disease

Introduction

Coeliac disease is a common but often under diagnosed gastrointestinal disorder. Its presentation is often vague and a low level of suspicion should be applied to anybody who presents with non-specific abdominal symptoms, and particularly in those with a family history of the disease.

It is a chronic, auto-immune like illness that occurs in genetically susceptible individuals. It is caused by an abnormal inflammatory response to the presence of gluten in the diet. This small bowel inflammation disappears when gluten is removed from the diet, and reappears if gluten is eaten again.

In susceptible individuals, exposure to gluten can lead to damage of the proximal small bowel. In serious cases, it can affect the whole bowel. Wheat, rye and barley all contain gluten – these are collectively referred to as prolamin.

Treatment involves a life-long gluten-free diet.

Epidemiology

• The prevalence of coeliac disease is about 1 in 50 to 1 in 100. However it is thought that less than half of cases are actually diagnosed
• Most common incidence is in children, and in those over 60, although it can occur at any age
• Slightly more common in women over 60 than in men over 60
• 30% risk for sibling, and 10% risk for first degree relatives, indicating an element of genetic susceptibility
• Associated with other autoimmune diseases
  • T1DM – about 8% of those with T2DM will also have coeliac disease.
  • Autoimmune thyroid disease
  • Addison’s

Pathology

Gluten is a protein, found in many grass-type foods. It gives starchy foods their chewy bread-like texture. In the intestine, gluten is broken down by tissue transglutaminases (tTG) into smaller constituents called gliadins. Antibodies against tTG and other substances are hallmarks of coeliac disease.

• Coeliac disease is a T-cell mediated auto-immune disease whereby a reaction against gluten eventually becomes an auto-immune reaction against the small intestinal mucosa.
• The cause of the initial reaction is unknown. However, it may be mediated by a viral infection, for example, the adenovirus 12 shows homology with gliadin.
• Gluten is a large molecule, that is broken down to smaller ones in the gut, and it is the breakdown products that are toxic (gliadins). The main toxic peptide is α-Gliadin.
• In coeliac disease there is production of two antibodies – anti-gliadin, and anti-endomysial. Anti endomysial antibody attacks tTG (tissue transglutaminase) which is the enzyme responsible for gluten breakdown.
• There is hypertrophy of crypts, and atrophy of the villi thus the overall wall thickness remains stable, but the surface of the bowel becomes flattened, and the surface area for absorption becomes greatly reduced
• Increase in the number of inflammatory cells in the lamina propria
• The proximal small intestine is most affected – due to the higher concentration of gluten products in this area (they get more broken down the further along the intestine they travel)

Symptoms

• About 25% of coeliac disease patients are initially diagnosed with IBS
• The mean time from presumed disease onset to diagnosis is about 10 years

Gastrointestinal symptoms

• General malaise / tiredness – often as a result of iron deficiency anaemia due to malabsorption
• Diarrhoea – due to malabsorption
• Nausea / vomiting
• Bloating
• Angular stomatitis – anaemia
• Weight loss
• Oral ulceration
• Osteomalacia

Non-GI manifestations

• Dermatitis Herpetiformis
  • About 20% patients will develop this rash. The rash tends to be very itchy and it found on the extensor surfaces of elbows and knees or on the trunk. The rash has a ‘herpetic’ appearance – looking like small vesicles, however in a truly heretic rash (as see in shingles, or HSV1 or 2 infection) the rash is often painful, and not itchy, as opposed to dermatitis herpetiformis which tends to be painless and itchy.
• Ataxia
  • About 50% of all “ataxia of unknown origin” patients are subsequently discovered to have coeliac disease. These symptoms are more likely to be permanent than other manifestations of coeliac disease

Children – The disease may present with weaning onto cereals. Symptoms will include diarrhoea (steatorrhea), malabsorption and failure to thrive.

Adults – In older children and adults it may present with more non-specific symptoms, such as failure to grow properly, or more vague symptoms, such as fatigue, abdominal pain, abdominal distension, iron-deficiency anaemia, (angular stomatitis), weight loss, and oral ulceration.

• Often the only sign is iron-deficiency anaemia.

• 1/3 of patients are asymptomatic.
• Skin rash – There is a very specific skin rash linked to coeliac disease.  It is called Dermatitis herpetiformis.

Investigations

Knowing whom to test for coeliac disease is a diagnostic challenge.

NICE recommends testing  patients (adults and children) with any of the following:

• Diarrhoea – chronic or intermittent
• Failure to thrive
• Irritable bowel syndrome
• Persistent, recurrent or unexplained nausea, vomiting, abdominal pain or bloating
• Sudden or unexpected weight loss
• Unexplained iron-deficiency  (or other) anaemia
• Autoimmune thyroid disease
• Type 1 diabetes
• Dermatitis herpetiformis
• First-degree relative with CD

• Blood Test for tissue Transglutaminase (tTG) IgA (anti-tTG).
  • Patients need to eat a diet containing gluten to return a positive tTG result. If they have been trialling a gluten free diet, they will need to eat at least 3g of gluten (approximately equivalent to 2 slices of bread) per day for at least two weeks to generate an inflammatory response in the small intestine, and at least 4 weeks for a positive blood result.
  • Anti-tTg is a type of IgA. 3% of patients with coeliac disease also have IgA deficiency and will return a false negative. If total IgA is low (usually the lab will perform this as well as the tTG) then testing deaminated gliadin peptide (DGP) can be tested to confirm the suspicion of serology evidence of coeliac disease
  • If positive tTG-IgA or DGP then refer to gastroenterology for duodenal biopsy to confirm that diagnosis
• HLA-DQ2/8 gene testing can be useful in certain circumstances.
  • About half the general population carry this gene variant
  • A positive test therefore is NOT diagnostic
  • However, a negative test has a strong negative predictive value (<1% of patients with negative test will have coeliac disease)
• Endoscopy to take a duodenal biopsy for histological examination (>4 samples should be taken) is required to confirm the diagnosis. 50% of those with positive antibody test may not have histological changes.
  • Serology alone is not enough to diagnose coeliac disease – confirmatory biopsy is required
• Histological findings typically involve: hypertrophy of the crypts, and atrophy of the villi, giving the mucosa a flattened appearance. The overall thickness of the mucosa is not changed. There must also be an increase in the number of inflammatory cells in the lamina propria for a diagnosis to be made. Also the receptors on T cells are different. Normally , they are of the γ δ type, but in coealic’s they become α β. This is specific to coeliacs, and is irreversible.
  • The changes seen in coeliacs are measured in the Marsh scale. This has 4 levels (I-IV, IV being the most severe), with most coeliacs patients being level III. Marsh type IV is associated with a non-response to a gluten-free diet, and thus has a much greater risk of complications.

Diagnosis

There are no set criteria for the diagnosis of coeliac disease, but typically you will need:

• Evidence of malabsorption (steatorrhoea, vitamin / nutritient deficiency)
• Villous atrophy on duodenal biopsy (this is the most specific diagnostic test)
• Weight loss
• Features resolve upon adoption of gluten free diet

Screening

There is a 10% risk of first degree relatives being affected (thought to be as high as 30% for siblings) and any symptomatic first degree relatives should be screened once other family members have been diagnosed.

Complications

• Nutritional deficiency due to malabsorption – particularly iron, B12 and folate
• Increase risk of some cancer – particularly lymphoma. Risk is less than previously thought. Those who have been following a gluten free diet for 3-5 years have same risk as the general population
• Reduced fertility (possibly) and increased risk of complications in pregnancy
• Osteopaenia – reduction in bone density – due to lack of calcium absorption. 
  • Consider early, and regular DEXA (bone density) scanning. Patients as young as 20 may have osteopenia. Scan within the first year of diagnosis and treat accordingly
• Osteoporosis – due to prolonged lack of calcium absorption
• Osteomalacia– due to vitamin D / calcium malabsorption
• Cerebellar disorders – due to problems with calcium metabolism
• Neurological disorders – e.g. parasthesia and muscle weakness
• Increased incidence of atopy other auto-immune conditions – particularly thyroid disease, type-1 diabetes etc.
• Increased risk of malignancy – GI lymphoma (rare) or can be oesophageal, gastric, brain or breast (these are even rarer). Also increased risk of T-cell lymphoma and MALT, although this is still rare.

Management

• Pasta
• Bread
• Cereals
• Biscuits
• Pastries / pies
• Crumbed foods
• Pizza
• Oats* <30g / day
  • many patients choose the avoid oats altogether
• Beware of additives – e.g. wheat based thickeners

• Rice
• Corn
• Meat
• Dairy products
• Fruit
• Vegetables

Many processed gluten free foods contain increased amounts of sugar and fat.

Symptoms start to resolves within weeks to months of a gluten free diet.

Weight gain and constipation are common in those adhering to a gluten free diet.

If symptoms remain at 18-24 months consider repeat endoscopy for a re-biopsy.

References

• Guideline for the diagnosis and management of Coeliac Disease in Children
• Diagnosing Coeliac Disease – the key facts
• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• RACGP – Check Cases – December 2017: Diet and Nutrition

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